Genomic Approaches for Detection and Treatment of Breast Cancer
Abstract
The evolution of human cells into malignant derivatives is driven by the aberrant function of genes that positively and negatively regulate various aspects of the cancer phenotype, including altered responses to mitogenic and cytostatic signals, resistance to programmed cell death, immortalization, neoangiogenesis, and invasion and metastasis (Hanahan and Weinberg, 2000). The integrity of these gene functions is compromised by substantial genetic and epigenetic alterations observed in most cancer cell genomes. To understand the tumorigenic process, it is imperative to identify and characterize the genes that provide tumor cells with the capabilities requisite for their initiation and progression. However, the identities of those genes that contribute to the tumor phenotype are often concealed by the frequent alterations in genes that play no role in tumorigenesis. Identifying genes that restrain tumorigenesis (tumor suppressors) has proven especially challenging due to their recessive nature. Further complicating their discovery are the multifaceted mechanisms by which tumor suppressor genes are inactivated including changes in copy number and structure, point mutations, and epigenetic alterations (Balmain et al., 2003). Moreover, the mechanisms by which tumor suppressor genes are inhibited may vary between tumors. With this in mind, a variety of molecular and cytogenetic technologies have been used to establish extensive catalogs of genetic alterations within human cancers (Albertson et al., 2003; Futreal et al., 2004). And while it is generally accepted that highly recurrent aberrations signify changes that are important for tumor development, the causal perturbations underlying tumor genesis are often confounded by the extensive size of alterations and the large number that are incidental to the tumor phenotypes. As such, new strategies to delineate genes with functional relevance to tumor initiation and development are essential to understanding
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA446731
Entities
People
- Stephen Elledge
Organizations
- Brigham and Women's Hospital